| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN4A | R1337P | Myotonia, sodium channel | High | 5 | 25088311 |
To assess whether the paralogue annotation here confidently predicts that variation at this residue is pathogenic, it is important to check the reports in the Pubmed links above to ascertain that the mutations in these paralogues have been proved likely to be disease-causing. It is also important to check that the direction of effect of the variant in the paralogue is compatible with your observed phenotype in SCN5A.
| SCN5A | ---KK-L----G-SKKP--------QKPIP>R<PLNKYQGFIFDIVTKQAFDVTIMFLICLNM | 1542 |
| SCN1A | ---KK-L----G-SKKP--------QKPIP>R<PGNKFQGMVFDFVTRQVFDISIMILICLNM | 1555 |
| SCN2A | ---KK-L----G-SKKP--------QKPIP>R<PANKFQGMVFDFVTKQVFDISIMILICLNM | 1545 |
| SCN3A | ---KK-L----G-SKKP--------QKPIP>R<PANKFQGMVFDFVTRQVFDISIMILICLNM | 1540 |
| SCN4A | ---KK-L----G-SKKP--------QKPIP>R<PQNKIQGMVYDLVTKQAFDITIMILICLNM | 1367 |
| SCN7A | ---KK-L----M-YEDS--------QRPVP>R<PLNKLQGFIFDVVTSQAFNVIVMVLICFQA | 1265 |
| SCN8A | ---KK-L----G-SKKP--------QKPIP>R<PLNKIQGIVFDFVTQQAFDIVIMMLICLNM | 1536 |
| SCN9A | ---KK-L----G-SKKP--------QKPIP>R<PGNKIQGCIFDLVTNQAFDISIMVLICLNM | 1518 |
| SCN10A | ---KK-L----G-SKKP--------QKPIP>R<PLNKFQGFVFDIVTRQAFDITIMVLICLNM | 1490 |
| SCN11A | ---KK-L----G-SKKP--------QKPIP>R<PLNKCQGLVFDIVTSQIFDIIIISLIILNM | 1380 |
| CACNA1A | ---DFAI------SAKP-------LTRHMP>Q<NKQSFQYRMWQFVVSPPFEYTIMAMIALNT | 1580 |
| CACNA1B | ---DFAI------SAKP-------LTRYMP>Q<NRQSFQYKTWTFVVSPPFEYFIMAMIALNT | 1486 |
| CACNA1C | ---EYAL------KARP-------LRRYIP>K<--NQHQYKVWYVVNSTYFEYLMFVLILLNT | 1233 |
| CACNA1D | ---EYAL------KARP-------LRRYIP>K<--NPYQYKFWYVVNSSPFEYMMFVLIMLNT | 1239 |
| CACNA1E | ---DFAI------SAKP-------LTRYMP>Q<NRHTFQYRVWHFVVSPSFEYTIMAMIALNT | 1492 |
| CACNA1F | ---EYAL------KAQP-------LRRYIP>K<--NPHQYRVWATVNSAAFEYLMFLLILLNT | 1204 |
| CACNA1G | L--DDVI-----ASGSSASAASEAQCKPYY>S<DYSRFRLLVHHLCTSHYLDLFITGVIGLNV | 1625 |
| CACNA1H | RLERRRRSTFPSPEAQ---------RRPYY>A<DYSPTRRSIHSLCTSHYLDLFITFIICVNV | 1631 |
| CACNA1I | RLEKKRR------KAQ---------RLPYY>A<TYCHTRLLIHSMCTSHYLDIFITFIICLNV | 1501 |
| CACNA1S | ---QYAL------KARP-------LRCYIP>K<--NPYQYQVWYIVTSSYFEYLMFALIMLNT | 1132 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R1512W | c.4534C>T | Inherited Arrhythmia | LQTS,BrS | rs137854602 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | BrS | Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome. Cardiovasc Res. 1999 44(3):507-17. 10690282 | ||
| Inherited Arrhythmia | BrS | Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes. Cardiovasc Res. 2000 46(1):55-65. 10727653 | |||
| Inherited Arrhythmia | BrS | Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing. Heart Rhythm. 2004 1(5):600-7. 15851227 | |||
| Inherited Arrhythmia | LQTS | Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm. 2009 6(3):341-8. 19251209 | |||
| Putative Benign | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | ||||
| Putative Benign | An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010 7(1):33-46. 20129283 | ||||
| Other Cardiac Phenotype | Loss-of-Function SCN5A Mutations Associated with Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture. Circ Arrhythm Electrophysiol. 2015 26111534 | ||||
| p.R1512Q | c.4535G>A | Putative Benign | rs368219299 | SIFT: deleterious Polyphen: possibly damaging | |
| p.R1512L | c.4535G>T | Putative Benign | SIFT: Polyphen: | ||